DESCRIPTION: The research proposed is an analysis of published data on mutagenesis, particularly data on changes in base sequence at mutations induced by various agents, to learn more about mechanisms of mutagenesis and to identify mutagenic agents. Some of these data are available in a database at Yale, and some in databases organized elsewhere. Topics for study include: the mechanism of formation and the mutagenic specificity of mutants with two mutations, such as a frameshift with an accompanying base change, mutants with two (or more) well-separated base changes and the spectra of mutations induced by hydrogen peroxide, superoxide radical, and singlet oxygen. Databases for sequence changes found in cancer-related genes (such as p53) from human and animal tumors will be searched for patterns of mutation that, on the basis of the analyses, can suggest particular chemicals or physical agents as the cause of the tumors. A review of damage induced in DNA by oxidizing species, including ionizing radiation, also is planned. The Yale database of mutational sequence changes will be considerably enlarged during this work, and it is hoped that it can be incorporated as part of a sequence database such as Genbank.